Characterization of complexes formed by polypropylene imine dendrimers and anti-HIV oligonucleotides

Abstract

Current anti-HIV therapies are capable of controlling viral infection but do not represent a definitive cure. They rely on the administration of antiretroviral nucleoside analogues, either alone or in combination with vectors. Dendrimers are branched, synthetic polymers with layered architectures, promising non-viral vectors in gene therapy. The aim of the paper was to study the interactions between three anti-HIV antisense oligonucleotides (ODNs): SREV, ANTI TAR, GEM91 and different generation polypropylene imine dendrimers (PPI) by monitoring changes in the fluorescence polarization of fluorescein attached to the ends of the ODNs when increasing concentrations of dendrimers were added. Laser Doppler electrophoresis, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to characterize, respectively, zeta potential, particle size and morphology of dendriplexes formed in different molar ratios. Antisense oligonucleotides interacted with polypropylene imine dendrimers in different molar ratios depending on generation. Zeta potential of dendriplexes varied from (-25 to -21) mV to -5 mV (for PPIG3 and PPIG4 complexes) and to zero (for PPIG2 complexes). The structures presented a polydisperse size from about 50 nm to even 700-800 nm by TEM and about 250 nm by DLS. It means that besides single dendriplexes, aggregates were also present.